EP0488218A2 - Procédé pour préparer des particules polymères - Google Patents

Procédé pour préparer des particules polymères Download PDF

Info

Publication number
EP0488218A2
EP0488218A2 EP91120279A EP91120279A EP0488218A2 EP 0488218 A2 EP0488218 A2 EP 0488218A2 EP 91120279 A EP91120279 A EP 91120279A EP 91120279 A EP91120279 A EP 91120279A EP 0488218 A2 EP0488218 A2 EP 0488218A2
Authority
EP
European Patent Office
Prior art keywords
polymer
particles
process according
derived
solidified
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP91120279A
Other languages
German (de)
English (en)
Other versions
EP0488218A3 (en
EP0488218B1 (fr
Inventor
John Kennedy
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
United States Surgical Corp
Original Assignee
United States Surgical Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by United States Surgical Corp filed Critical United States Surgical Corp
Publication of EP0488218A2 publication Critical patent/EP0488218A2/fr
Publication of EP0488218A3 publication Critical patent/EP0488218A3/en
Application granted granted Critical
Publication of EP0488218B1 publication Critical patent/EP0488218B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/12—Powdering or granulating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B9/00—Making granules
    • B29B9/10—Making granules by moulding the material, i.e. treating it in the molten state
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L23/00—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
    • C08L23/02—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers not modified by chemical after-treatment
    • C08L23/10—Homopolymers or copolymers of propene
    • C08L23/12—Polypropene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L27/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers
    • C08L27/02—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment
    • C08L27/12—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment containing fluorine atoms
    • C08L27/18—Homopolymers or copolymers or tetrafluoroethene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L69/00—Compositions of polycarbonates; Compositions of derivatives of polycarbonates
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L77/00—Compositions of polyamides obtained by reactions forming a carboxylic amide link in the main chain; Compositions of derivatives of such polymers
    • C08L77/02—Polyamides derived from omega-amino carboxylic acids or from lactams thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
    • C08J2367/02—Polyesters derived from dicarboxylic acids and dihydroxy compounds

Definitions

  • This invention relates to a process for preparing particles of polymer, e.g., spheroidal particulates or beads of the bioabsorbable variety, employing various individual atomization techniques such as melt extrusion and/or rotary atomization.
  • the particles are useful, inter alia , in the repair of damaged or defective bone.
  • polymer particles including those of the bioabsorbable variety are known, inter alia , from U.S. Patent Nos. 3,882,858; 4,535,485; 4,547,390; 4,643,735; and 4,663,447.
  • U.S. Patent Nos. 3,882,858; 4,535,485; 4,547,390; 4,643,735; and 4,663,447 There has been an increase in interest in utilizing both bioabsorbable and non-absorbable particles to facilitate bone or fibrous tissue repair/reconstruction.
  • a number of processes are contemplated for preparing finely divided polymeric particles, e. g., mechanical grinding, solvent precipitation, dispersion, spray atomization of solutions or slurries, and rotary atomization.
  • rotary atomization the polymer is applied to a rotation bell, cup or disk with mechanical forces predominating in the breakup of the polymer into particles.
  • the Applicants have themselves previously proposed a process for preparing foamed, bioabsorbable polymer particles by a freeze-drying technique (US patent application 503,264).
  • microspheres of absorbable material less than or equal to 0.2 mm in diameter for use in controlled release of drugs are well-known. Such spheres have generally been formed by a solvent evaporation technique. Alternatively, polymeric microspheres, e.g., beads, of average particle size greater than or equal to 0.2 mm in diameter can be formed by an emulsion polymerization process. Such emulsion polymerization has been successfully utilized to form beads of polymethylmethacrylate and styrene.
  • the present invention is directed to a process for preparing particles from a polymer having fiber-forming properties comprising:
  • particles of polymer of substantially uniform size e.g., microspheres of about 0.1 to about 3.0 mm average size (in diameter) can be prepared from polymeric substances, while fiber forming tendencies of the polymer are suppressed.
  • the fiber forming tendency of the polymeric material which is believed to relate to the surface tension exhibited by the polymer, is inhibited according to the present invention such that substantially no fibers are produced among the particles that are prepared.
  • the term "fiber” refers to materials which may be characterized as having a denier (see, e.g., Plastics Terms Glossary , Fourth Edition , Phillips Chemical Company, Bartlesville, Oklahoma).
  • the particles are preferably formed into spheres which can be used as a packing or molded part in dental or orthopedic applications in which a bony defect is filled with material. Such material then acts as a scaffold for new bony ingrowth while, in the case of bioabsorbable particles, being resorbed by the body, leaving behind a fully healed bone tissue structure.
  • a polymer is selected for processing which has an inherent viscosity not exceeding about 0.6 dl/g when measured at a temperature of about 30°C in chloroform or HFIP (concentration of the polymer during this measurement is about 0.25 g/dl).
  • HFIP is generally used as the measuring solvent when glycolide content exceeds about 40 mole percent of the overall polymer being measured.
  • the polymer has an inherent viscosity, when measured under these conditions, of about 0.2 to about 0.5 dl/g, more preferably about 0.25 to about 0.45 dl/g.
  • the polymer can have an initial inherent viscosity within the levels set forth above.
  • the polymer can have an initial inherent viscosity exceeding about 0.6 dl/g when measured under the above conditions and then can be treated, e.g., heated, to cause degradation of the polymer, such as by hydrolysis (when heated in the presence of moisture), to reduce the viscosity to the levels set forth above.
  • the polymer can then be further heated in accordance with the heating step of the present invention.
  • the polymer possessing an inherent viscosity not exceeding about 0.6 dl/g when measured under the above conditions exhibits a reduced tendency to form fibers because of a physical attribute associated with the polymer, e.g., an increased surface tension and/or reduced chain lengths of individual polymer chains relative to higher inherent viscosity materials.
  • the inherent viscosity is a function of, among other factors, the molecular weight of a polymer. Accordingly, the inherent viscosity of the polymer can be controlled by selecting a polymer having an appropriate molecular weight.
  • the polymer is preferably bioabsorbable and can be derived from polyglycolic acid, glycolide, lactic acid, lactide, dioxanone, e-caprolactone, trimethylene carbonate, etc., and various combinations of these and related monomers. Polymers of this type are known in the art, principally as materials for the fabrication of such surgical devices as sutures, wound clips, and the like, as disclosed, e.g., in U.S. Patent Nos.
  • the present invention may also be practiced on non-absorbable polymeric materials having fiber-forming properties such as nylon, polyester, polypropylene, polytetrafluoroethylene (PTFE), polyethylene terephthalate (Dacron), etc.
  • non-absorbable polymeric materials having fiber-forming properties such as nylon, polyester, polypropylene, polytetrafluoroethylene (PTFE), polyethylene terephthalate (Dacron), etc.
  • the polymeric material is heated so as to produce a flowable mass.
  • the polymer is preferably heated to a temperature from about 60°C to about 300°C. More particularly, the temperature to which the polymeric material will be heated, will depend on the melt characteristics of the polymer selected. For example, for a glycolide/lactide copolymer, the system is heated to a temperature of from about 100 to about 300°C, preferably from about 170°C to about 270°C, and most preferably from about 220°C to about 250°C. For polymers having lower melting points, e.g., polycaprolactone, lower temperatures may be employed, e.g., about 60°C, whereas higher temperature may be required for materials having higher melting points.
  • the heated molten polymer is divided into particles with the molten particles then being solidified.
  • the polymer is divided and solidified into the particles such that an average particle size (diameter) of the particles when solidified will be from about 0.1 to about 3 mm, more preferably from about 0.2 mm to about 1.5 mm, and most preferably from about 0.3 to about 1.0 mm.
  • the molten polymer can be divided, e.g., into droplets, by being extruded through a capillary provided in an extrusion die of extrusion apparatus.
  • Suitable extrusion apparatus which can be utilized in accordance with the present invention are described in G.A. Kruder, "Extrusion”, Encyclopedia of Polymer Science and Engineering (Second Edition ), Volume 6, pages 571-631, and in P. N. Richardson, "Plastics Processing", Encyclopedia of Chemical Technology (Third Edition ), Volume 18, pages 185-189. Any part of the extrusion apparatus such as the extruder screw or the capillary die can be heated to the appropriate temperature in order to heat the polymer.
  • an Instron Rheometer available from the Instron Corp. of Canton, Massachusetts 02021 can be used.
  • the Instron Rheometer has an extrusion barrel of about 20 cm3 capacity and which is provided with a capillary die at the bottom thereof. The barrel is heated to the appropriate temperature and then loaded with the polymer, which is forced down through the capillary die by means of a plunger extending into the barrel.
  • Extrusion can be carried out through a capillary die adapter 1 illustrated in Fig. 1, having a capillary 2 of substantially constant inner diameter h.
  • a capillary die adapter 20 of Fig. 2 can be utilized, which comprises a capillary 12 of narrowing inner diameter. Rate of extrusion and diameter size of the capillary determine ultimate particle size of solidified polymer particles.
  • the capillary has a narrowest inner diameter of preferably about 0.010 to about 0.002 inch, more preferably about 0.009 to about 0.003 inch, and most preferably about 0.008 to about 0.004 inch.
  • the polymer is extruded through the capillary preferably at a rate of about 15 to about 0.3 inch/min., more preferably at a rate of about 12 to about 0.5 inch/min., and most preferably at a rate of about 10 to about 1 inch/min.
  • the molten polymer can be divided into droplets, after being heated, by being sprayed through a spray nozzle.
  • the spray nozzle itself can be heated to an appropriate temperature level in order to heat the polymer.
  • the polymer can also be divided, after heating, by being applied onto a rotary atomizer upon whose surface the polymer breaks up into particles which are thrust away from the axis of the rotary atomizer.
  • Suitable rotary atomizers which can be utilized in accordance with the present invention include those disclosed in U.S. Patent Nos. 4,256,677; 3,741,703; and 3,743,464.
  • a circular rotating element e.g. a spinning disk of the rotary atomizer, can be flat, convex, concave, or even bell-shaped, and can contain protruding vanes on a surface thereof.
  • the size of the spinning disk itself and the rpm., i.e. rate of rotation, can be interrelated to provide the optimum centrifugal acceleration for the formation of the particles of bioabsorbable polymer. Variations of this centrifugal acceleration will affect the ultimate size of the particles that are formed.
  • the revolutions of the spinning disk are controlled within a range of preferably about 100 to about 1000 rpm., more preferably within a range of about 130 to about 850 rpm., and most preferably within a range of about 160 to about 700 rpm.
  • the disk itself is preferably between about 66 and about 86 cm. in diameter, more preferably between about 71 and about 81 cm. in diameter, and most preferably between about 75 and about 77 cm. in diameter.
  • the instantaneous velocity of the disk is preferably controlled within a range of about 4 to about 40 m./sec., more preferably within a range of about 5 to about 35 m./sec., and most preferably within a range of about 6 to about 28 m./sec.
  • the bioabsorbable polymer is supplied in the form of a thin film onto a surface of the spinning disk of the rotary atomizer, whereby the centrifugal acceleration breaks the thin film into particles of the bioabsorbable polymer.
  • this film of polymer is applied about 0.01 to about 3.5 mm. thick on the spinning disk, more preferably about 0.1 to about 3.2 mm. thick, and most preferably of about 1.0 to about 3.0 mm. thick.
  • Surface tension will cause the resulting particles of broken up polymer to ultimately harden into particles which are spheroidal or in the shape of beads, as these particles are radially discharged from the disk, i.e. fall off the edge of the rotary spinning disk of the rotary atomizer and are cooled. Varying the film thickness on the spinning disk or varying the feed rate of the flowable bioabsorbable polymer affects particle size, with the thinnest film causing the smallest particles to be formed.
  • the molten polymer can be divided by other means within the context of the present invention. Once divided, the molten particles of polymer are solidified. Solidification can be carried out by allowing the extruded, sprayed or atomized particles to fall into a liquid which is immiscible with the molten polymer, which freezes the polymer particles on contact therewith, and in which the solidified polymer is not soluble.
  • the freezing liquid can be, e.g., liquid nitrogen, and mixtures of solid carbon dioxide and a liquid such as acetone, pentane, etc. In general, the temperature of the freezing liquid is advantageously at least about 10°C below the freezing temperature of the polymer particles.
  • the particles of frozen polymer can be recovered from the freezing liquid employing any suitable means, e.g., draining, straining, filtering, decanting or centrifuging, and the like. This operation is conducted at or below the melting point of the frozen polymeric particles to maintain the particles in the frozen state.
  • the polymeric particles can be solidified by falling freely through the air.
  • the particles are allowed to fall a distance of at least about 40 cm. through the air, whereby the particles are sufficiently cooled before striking a collecting unit so that the particles will not stick together upon striking the collecting unit. More specifically, the particles are allowed to fall a distance of preferably about 190 to about 254 cm., more preferably about 200 to about 240 cm., and most preferably about 215 to about 230 cm. before striking the collecting unit.
  • the collecting unit may be provided, e.g., as disclosed in U.S. Patent Nos. 4,256,677 and 3,743,464.
  • the particles or beads formed of bioabsorbable or non-absorbable polymers can be used as filler in a surgical prosthesis, i.e. for implantation in a cavity provided in bone or fibrous tissue to encourage regrowth and regeneration of the tissue.
  • the particles of the bioabsorbable polymer are absorbed by the body at a predictable rate allowing tissue or bony ingrowth as absorption takes place. The rate of absorption is characteristic of the polymer utilized.
  • a glycolide-lactide copolymer will often completely resorb within six months in contrast to about two years for polyglycolide homopolymer.
  • Both the bioabsorbable and non-absorbable polymeric particles are readily molded to fill cavities or other contours.
  • the beads can be heated to softening temperature, e.g., to about 60°C, at which temperature they can be worked and shaped.
  • any required drug, medicinal material, or growth factor can be incorporated into the polymer prior to processing, e.g. by addition to the polymer in the customary amounts so that at the conclusion of the polymeric particle manufacturing process herein, the particles will contain a predetermined amount of one or more of such substances.
  • the polymer particles can carry a therapeutic agent which will be deposited at the repair site.
  • the therapeutic agent can be chosen for its antimicrobial properties, capability for promoting repair or reconstruction and/or new tissue growth or for specific indications such as thrombosis.
  • Antimicrobial agents such as broad spectrum antibiotics (gentamicin sulphate, erythromycin or derivatized glycopeptides) which are slowly released into the tissue can be applied in this manner to aid in combating clinical and sub-clinical infections in a tissue repair site.
  • one or several growth promoting factors can be introduced into the particles, e.g., fibroblast growth factor, bone growth factor, epidermal growth factor, platelet derived growth factor, macrophage derived growth factor, alveolar derived growth factor, monocyte derived growth factor, magainin, and so forth.
  • Some therapeutic indications are: glycerol with tissue or kidney plasminogen activator to cause thrombosis, superoxide dismutase to scavenge tissue damaging free radicals, tumor necrosis factor for cancer therapy or colony stimulating factor and interferon, interleukin-2 or other lymphokine to enhance the immune system.
  • This copolymer was maintained in the barrel of the extrusion apparatus for 5 minutes and then extruded through capillary 2 of the die adapter 1 at a rate of 0.3 inch/min., whereby droplets of the polymer were formed. These droplets of the polymer were allowed to fall from the die adapter 1 a distance of 40 cm. and into a vat of liquid nitrogen at a temperature of -196°C., with the droplets of polymer thereby solidifying into beads. The beads were collected from the liquid nitrogen, classified, and were found to have an average diameter of 3 mm. The solidified polymer thus formed was substantially free of fibers.
  • Example 1 The procedure of Example 1 was repeated, but with a die adapter disc 10 of Fig. 2 having a capillary 12 necking down from an inner entrance diameter D' of 1.25 mm to an inner exit diameter d' of 0.008 inch, with the extrusion apparatus including the adapter 10 being heated to a temperature of 225°C, and with respective rates of extrusion of 1 inch/min., 3 inch/min., and 10 inch/min. respectively for equal extruded amounts of the 25/75 mole percent glycolide/lactide copolymer having an inherent viscosity of 0.5 dl/g measured at 30°C in HFIP and at a concentration of 0.25 g/dl.
  • 16 sieve has openings of 1.19 mm; a No. 18 sieve has openings of 1.00 mm; a No. 20 sieve has openings of 0.841 mm; a No. 25 sieve has openings of 0.707 mm; and a No. 40 sieve has openings of 0.420 mm.
  • Example 2 The procedure of Example 2 was repeated but with all molten polymer being extruded at a rate of 1 inch/min. A total of 6.96 g of beads was collected and then classified, with the distribution being reported in Table III below: Table III Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 14 0.84 12.07 16 1.71 24.57 18 1.99 28.59 20 1.83 26.29 25 0.25 3.59 40 0.30 4.31 Passed Through 40 0.04 0.58 Total 6.96 ⁇ g Total 100.00 ⁇ %
  • Example 2 The procedure of Example 2 was repeated, but with all molten polymer being extruded at a rate of 3 inches/min. A total of 13.03 g of beads was collected and then classified, with the distribution being reported in Table IV below: Table IV Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 14 9.93 76.21 16 2.30 17.65 18 0.64 4.91 20 0.06 0.46 25 0.07 0.54 40 0.02 0.15 Passed Through 40 0.01 0.08 Total 13.03 ⁇ g Total 100.00 ⁇ %
  • Example 2 The procedure of Example 2 was repeated, but with all molten polymer being extruded at a rate of 10 inches/min. A total of 19.62 g of beads was collected and then classified, with the distribution being reported in Table V below: Table V Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 14 13.49 68.76 16 3.38 17.23 18 1.35 6.88 20 0.63 3.21 25 0.38 1.94 40 0.32 1.63 Passed Through 40 0.07 0.36 Total 19.62 ⁇ g Total 100.01 ⁇ %** **100.01% value due to rounding of significant figures.
  • Example 3 The procedure of Example 3 was repeated in its entirety, but with the molten polymer being extruded through die adapter 10 having an extrusion channel 12 necking down from an entrance diameter D' of 1.25 mm to a minimum a diameter d' of 0.006 inch at the outlet thereof.
  • a total of 5.94 g of beads was collected and then classified, with the distribution being reported in Table VI below: Table VI Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 14 0.70 11.78 16 1.09 18.35 18 1.45 24.41 20 1.17 19.70 25 0.88 14.82 40 0.58 9.76 Passed Through 40 0.07 1.18 Total 5.94 ⁇ g Total 100.00 ⁇ %
  • Example 4 The procedure of Example 4 was repeated in its entirety, but with the molten polymer being extruded through die adapter 10 having an extrusion channel 12 necking down from an entrance diameter D' of 1.25 mm to a minimum diameter d' of 0.006 inch at the outlet thereof. A total of 8.49 g of beads was collected and then classified, with the distribution being reported in Table VII below: Table VII Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 14 2.58 30.39 16 2.89 34.04 18 2.15 25.32 20 0.39 4.59 25 0.23 2.71 40 0.18 2.12 Passed Through 40 0.07 0.83 Total 8.49 ⁇ g Total 100.00 ⁇ %
  • Example 5 The procedure of Example 5 was repeated in its entirety, but with the molten polymer being extruded through a die adapter 10 having an extrusion channel 12 necking down from an entrance diameter D' of 1.25 mm to a minimum diameter d' of 0.006 inch at the outlet thereof. A total of 14.5 g of beads was collected and then classified, with the distribution being reported in Table VIII below: Table VIII Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 14 5.63 38.83 16 5.06 34.90 18 1.52 10.48 20 0.72 4.96 25 0.82 5.66 40 0.63 4.34 Passed through 40 0.12 0.83 Total 14.50 ⁇ g Total 100.00 ⁇ %
  • Example 2 The procedure of Example 2 was repeated in its entirety, but with the molten polymer additionally being stirred before extrusion. A total of 56.77 g of beads was collected and then classified, with the distribution being reported in Table IX below: Table IX Sieve No. Weight (g) of Particles Retained Thereon % of Particles Retained Thereon 14 22.36 39.39 16 17.00 29.95 18 11.78 20.75 20 1.99 3.51 25 1.66 2.92 40 1.62 2.85 Passed Through 40 0.36 0.63 Total 56.77 ⁇ g Total 100.00 ⁇ %
  • Example 2 The procedure of Example 2 was repeated in its entirety, but with a die 10 having a channel 12 necking down from an entrance diameter D' of 1.25 mm to a minimum exit diameter d' of 0.006 inch. A total of 7.61 g of beads was collected and then classified, with the distribution being reported in Table X below: Table X Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 20 0.32 4.20 25 3.72 48.88 40 3.39 44.55 Passed through 40 0.18 2.37 Total 7.61 ⁇ g Total 100.00 ⁇ %
  • Example 7 The procedure of Example 7 was repeated in its entirety, but with polyglycolic acid (PGA), having an inherent viscosity of 0.25 dl/g measured at 30°C in HFIP and at a concentration of 0.25 g/dl, being heated to 225°C and then being extruded at a rate of 3 inch/min. A total of 10.04 g of PGA beads was collected and then classified, with the distribution being reported in Table XI below: Table XI Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 20 6.30 62.75 25 1.80 17.93 40 1.70 16.93 Passed Through 40 0.24 2.39 Total 10.04 ⁇ g Total 100.00 ⁇ %
  • Example 11 The procedure of Example 11 was repeated, but with the polyglycolic acid (PGA) being heated to 240°C and then being extruded (the PGA had an inherent viscosity of 0.25 dl/g at 30°C in HFIP and at a concentration of 0.25 g/dl). A total of 5.52 g of PGA beads was collected and then classified, with the results being reported in Table XII below: Table XII Sieve No. Weight (g) of Particles Retained Thereon % Particles Retained Thereon 20 4.90 88.77 25 0.22 3.98 40 0.31 5.62 Passed Through 40 0.09 1.63 Total 5.52 ⁇ g Total 100.00 ⁇ %
EP91120279A 1990-11-27 1991-11-27 Procédé pour préparer des particules polymères Expired - Lifetime EP0488218B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US07/618,652 US5342557A (en) 1990-11-27 1990-11-27 Process for preparing polymer particles
US618652 2000-07-18

Publications (3)

Publication Number Publication Date
EP0488218A2 true EP0488218A2 (fr) 1992-06-03
EP0488218A3 EP0488218A3 (en) 1992-08-12
EP0488218B1 EP0488218B1 (fr) 1997-07-09

Family

ID=24478573

Family Applications (1)

Application Number Title Priority Date Filing Date
EP91120279A Expired - Lifetime EP0488218B1 (fr) 1990-11-27 1991-11-27 Procédé pour préparer des particules polymères

Country Status (4)

Country Link
US (1) US5342557A (fr)
EP (1) EP0488218B1 (fr)
CA (1) CA2056055A1 (fr)
DE (1) DE69126766T2 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0499205A2 (fr) * 1991-02-12 1992-08-19 United States Surgical Corporation Procédé pour préparer de particules de polymères bioabsorbables
EP0574880A1 (fr) * 1992-06-15 1993-12-22 United States Surgical Corporation Procédé de traitement d'une matière d'implantation bioabsorbable
US5342557A (en) * 1990-11-27 1994-08-30 United States Surgical Corporation Process for preparing polymer particles
EP1044693A1 (fr) * 1997-12-29 2000-10-18 Takiron Co., Ltd. Une substance polymère biorésorbable, argileuse et collante
AU782328B2 (en) * 1999-04-16 2005-07-21 Takiron Co. Ltd. Bioresorbable polymeric clayey and sticky substance
WO2007054267A1 (fr) * 2005-11-10 2007-05-18 Airbus Deutschland Gmbh Procede de manipulation d'un liquide
EP1923187A1 (fr) * 2006-11-14 2008-05-21 Linde Aktiengesellschaft Dispositif et procédé pour la génération de particules
EP1923188A1 (fr) * 2006-11-14 2008-05-21 Linde Aktiengesellschaft Dispositif de production de particule
EP3040378A4 (fr) * 2013-08-29 2016-08-31 Lg Hausys Ltd Composition de résine à expanser pour feuille de mousse, feuille de mousse, procédé de production d'une résine d'acide polylactique particulaire, et procédé de fabrication d'une feuille de mousse
JP2017504707A (ja) * 2014-07-17 2017-02-09 ウルトラ ヴイ カンパニー リミテッド フィラー用ポリジオキサノン粒子の製造方法

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5599852A (en) * 1994-10-18 1997-02-04 Ethicon, Inc. Injectable microdispersions for soft tissue repair and augmentation
US6287499B1 (en) 1998-10-09 2001-09-11 United States Surgical Corporation Process of making bioabsorbable block copolymer filaments
JP2001064400A (ja) * 1999-06-22 2001-03-13 Mitsui Chemicals Inc ポリヒドロキシカルボン酸の製造方法
US9080146B2 (en) 2001-01-11 2015-07-14 Celonova Biosciences, Inc. Substrates containing polyphosphazene as matrices and substrates containing polyphosphazene with a micro-structured surface
US8545386B2 (en) * 2003-08-14 2013-10-01 Boston Scientific Scimed, Inc. Surgical slings
WO2005016184A1 (fr) 2003-08-14 2005-02-24 Scimed Life System, Inc. Bandelettes chirurgicales
US9107850B2 (en) 2004-10-25 2015-08-18 Celonova Biosciences, Inc. Color-coded and sized loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same
US20210299056A9 (en) 2004-10-25 2021-09-30 Varian Medical Systems, Inc. Color-Coded Polymeric Particles of Predetermined Size for Therapeutic and/or Diagnostic Applications and Related Methods
AU2005298344B2 (en) 2004-10-25 2011-02-10 Varian Medical Systems, Inc. Loadable polyphosphazene-comprising particles for therapeutic and/or diagnostic applications and methods of preparing and using the same
US9114162B2 (en) 2004-10-25 2015-08-25 Celonova Biosciences, Inc. Loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same
BRPI0609874B1 (pt) * 2005-04-27 2018-02-27 Polymetrix Ag Processo para produção de partículas de poliéster
US20080075777A1 (en) * 2006-07-31 2008-03-27 Kennedy Michael T Apparatus and methods for preparing solid particles
US8735504B2 (en) * 2012-05-02 2014-05-27 Warsaw Orthopedic, Inc. Methods for preparing polymers having low residual monomer content

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1298121A (en) * 1969-04-24 1972-11-29 Basf Ag Method for making powdered thermoplastics
US4165420A (en) * 1977-11-10 1979-08-21 The Goodyear Tire & Rubber Company Solid state polymerization of polyester prepolymer
EP0052793A1 (fr) * 1980-11-24 1982-06-02 E.I. Du Pont De Nemours And Company Granules d'oligomère de térephtalate d'éthylène
EP0058481A1 (fr) * 1981-02-16 1982-08-25 Zeneca Limited Compositions pharmaceutiques pour la libération continue de la substance active
US4384975A (en) * 1980-06-13 1983-05-24 Sandoz, Inc. Process for preparation of microspheres
US4523591A (en) * 1982-10-22 1985-06-18 Kaplan Donald S Polymers for injection molding of absorbable surgical devices
CH661206A5 (fr) * 1983-09-23 1987-07-15 Debiopharm Sa Procede pour la preparation d'un medicament destine au traitement de maladies hormonodependantes.
EP0237345A2 (fr) * 1986-03-12 1987-09-16 Washington University Technology Associates, Inc. Méthode et appareil de granulation et produit granulé
EP0283925A2 (fr) * 1987-03-19 1988-09-28 Boehringer Ingelheim Kg Procédé de purification de polyester résorbable
US4822534A (en) * 1987-03-05 1989-04-18 Lencki Robert W J Method of producing microspheres
WO1992000342A1 (fr) * 1990-07-02 1992-01-09 Courtaulds Coatings (Holdings) Limited Compositions pulverulentes de revetement et procede de fabrication

Family Cites Families (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL27947A (en) * 1967-05-09 1972-07-26 Weitzman J Method for the production of thermoplastic resin particles and of mixtures of such particles with additives
DE2032712C3 (de) * 1970-07-02 1978-10-19 Bayer Ag, 5090 Leverkusen Verfahren zur Herstellung von w-Amino-alkanphosphonsäure bzw.- phosphinsäurederivaten
US3741703A (en) * 1971-04-26 1973-06-26 Lilly Industries Ltd An apparatus for making spherical granules
US3743464A (en) * 1971-08-24 1973-07-03 Fmc Corp Continuous sphering apparatus
DE2320373B2 (de) * 1973-04-21 1978-04-06 Merck Patent Gmbh, 6100 Darmstadt Antibioticahaltiges Mittel und seine Verwendung als chirurgisches Kunststoffmaterial
NL7509293A (nl) * 1975-08-05 1977-02-08 Stamicarbon Inrichting voor het bereiden van polymeren met een brede molecuulgewichtsverdeling.
US3981957A (en) * 1975-08-06 1976-09-21 Exxon Research And Engineering Company Process for preparing finely divided polymers
US4256677A (en) * 1976-04-12 1981-03-17 Magnavox Government And Industrial Electronics Co. Apparatus and method for making small spheres
US4186448A (en) * 1976-04-16 1980-02-05 Brekke John H Device and method for treating and healing a newly created bone void
US4100236A (en) * 1976-11-16 1978-07-11 The Continental Group, Inc. Method of preparing micron size particles of solid polymers
JPS5523711A (en) * 1978-07-29 1980-02-20 Sony Corp Rotary electric machine
US4200601A (en) * 1978-08-17 1980-04-29 National Distillers And Chemical Corporation Process of preparing finely divided polyolefin resins
JPS5940054B2 (ja) * 1978-08-29 1984-09-27 株式会社佐藤技術研究所 融体から特定サイズの球形粒子を製造する方法
US4933105A (en) * 1980-06-13 1990-06-12 Sandoz Pharm. Corp. Process for preparation of microspheres
US4336210A (en) * 1980-11-10 1982-06-22 National Distillers & Chemical Corp. Process for the preparation of finely divided thermoplastic resin
US4329304A (en) * 1980-11-10 1982-05-11 National Distillers & Chemical Corp. Process for the preparation of finely divided thermoplastic resin
US4436782A (en) * 1980-11-24 1984-03-13 E. I. Du Pont De Nemours And Company Oligomer pellets of ethylene terephthalate
DE3128872A1 (de) * 1981-07-22 1983-02-10 Basf Ag, 6700 Ludwigshafen Verfahren zur reproduzierbaren herstellung von formteilchen unterschiedlicher geometrie aus polymerdispersionen, schmelzen oder loesungen
US4430451A (en) * 1982-03-03 1984-02-07 The United States Of America As Represented By The United States Department Of Energy Low density, microcellular foams, preparation, and articles
US4535485A (en) * 1982-03-12 1985-08-20 Medical Biological Sciences, Inc. Polymeric acrylic prothesis
US4547390A (en) * 1982-03-12 1985-10-15 Medical Biological Sciences, Inc. Process of making implantable prosthesis material of modified polymeric acrylic (PMMA) beads coated with PHEMA and barium sulfate
GB2121203B (en) * 1982-04-06 1985-10-16 Canon Kk Making toner particles
FR2537980B1 (fr) * 1982-12-17 1986-12-19 Sandoz Sa Derives d'acides hydroxycarboxyliques oligomeres, leur preparation et leur utilisation
US4734227A (en) * 1983-09-01 1988-03-29 Battelle Memorial Institute Method of making supercritical fluid molecular spray films, powder and fibers
JPS6090229A (ja) * 1983-10-24 1985-05-21 Japan Styrene Paper Co Ltd ポリエチレン系樹脂発泡粒子
JPS60155245A (ja) * 1984-01-24 1985-08-15 Daicel Chem Ind Ltd 酢酸セルロ−ス多孔質球状粒子及びその製造方法
KR920006865B1 (ko) * 1984-05-18 1992-08-21 워싱톤 유니버시티 테크놀러지 어소우시에이츠 인코오퍼레이티드 입자나 액적을 피복하는 방법과 장치
US4578502A (en) * 1985-01-22 1986-03-25 Cudmore Warner J G Polyethylene terephthalate saponification process
US4643735A (en) * 1985-02-27 1987-02-17 Hayes Separation, Inc. Repair material for use with bones
US4693986A (en) * 1985-06-25 1987-09-15 Orthomatrix, Inc. Ceramic process and products
SE459005B (sv) * 1985-07-12 1989-05-29 Aake Rikard Lindahl Saett att framstaella sfaeriska polymerpartiklar
US4673695A (en) * 1985-10-08 1987-06-16 The United States Of America As Represented By The United States Department Of Energy Low density microcellular foams
US4701289A (en) * 1985-11-08 1987-10-20 Dow Corning Corporation Method and apparatus for the rapid solidification of molten material in particulate form
US4648820A (en) * 1985-11-14 1987-03-10 Dresser Industries, Inc. Apparatus for producing rapidly quenched metal particles
JPS62223112A (ja) * 1986-03-25 1987-10-01 Rooto Seiyaku Kk 歯周病治療剤
US5160745A (en) * 1986-05-16 1992-11-03 The University Of Kentucky Research Foundation Biodegradable microspheres as a carrier for macromolecules
DE3787700T3 (de) * 1986-10-29 1998-12-24 Kanegafuchi Chemical Ind Gleichförmige Polymerteilchen.
EP0265906B1 (fr) * 1986-10-31 1995-04-19 Nippon Zeon Co., Ltd. Pansement
DE3644588C1 (de) * 1986-12-27 1988-03-10 Ethicon Gmbh Implantat und Verfahren zu seiner Herstellung
US5047180A (en) * 1987-07-24 1991-09-10 Hoechst Celanese Corporation Process for making cellulose ester microparticles
FR2623402B1 (fr) * 1987-11-19 1994-04-29 Solvay Article en polymere d'acide lactique utilisable notamment comme prothese biodegradable et procede pour sa realisation
US5047450A (en) * 1988-04-05 1991-09-10 Phillips Petroleum Company Polyethylene terephthalate molding resin blends
US4940734A (en) * 1988-11-23 1990-07-10 American Cyanamid Process for the preparation of porous polymer beads
US5128114A (en) * 1989-04-14 1992-07-07 E. I. Du Pont De Nemours And Company Silica microspheres, method of improving attrition resistance
US5019400A (en) * 1989-05-01 1991-05-28 Enzytech, Inc. Very low temperature casting of controlled release microspheres
DE3931417A1 (de) * 1989-09-21 1991-04-04 Bayer Ag Rutilmischphasenpigment-mikrogranulate, verfahren zu ihrer herstellung sowie deren verwendung
US5080994A (en) * 1989-10-23 1992-01-14 Xerox Corporation Processes for the preparation of particles
US5102983A (en) * 1990-04-02 1992-04-07 United States Surgical Corporation Process for preparing foamed, bioabsorbable polymer particles
US5342557A (en) * 1990-11-27 1994-08-30 United States Surgical Corporation Process for preparing polymer particles
US5143662A (en) * 1991-02-12 1992-09-01 United States Surgical Corporation Process for preparing particles of bioabsorbable polymer

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1298121A (en) * 1969-04-24 1972-11-29 Basf Ag Method for making powdered thermoplastics
US4165420A (en) * 1977-11-10 1979-08-21 The Goodyear Tire & Rubber Company Solid state polymerization of polyester prepolymer
US4384975A (en) * 1980-06-13 1983-05-24 Sandoz, Inc. Process for preparation of microspheres
EP0052793A1 (fr) * 1980-11-24 1982-06-02 E.I. Du Pont De Nemours And Company Granules d'oligomère de térephtalate d'éthylène
EP0058481A1 (fr) * 1981-02-16 1982-08-25 Zeneca Limited Compositions pharmaceutiques pour la libération continue de la substance active
US4523591A (en) * 1982-10-22 1985-06-18 Kaplan Donald S Polymers for injection molding of absorbable surgical devices
CH661206A5 (fr) * 1983-09-23 1987-07-15 Debiopharm Sa Procede pour la preparation d'un medicament destine au traitement de maladies hormonodependantes.
EP0237345A2 (fr) * 1986-03-12 1987-09-16 Washington University Technology Associates, Inc. Méthode et appareil de granulation et produit granulé
US4822534A (en) * 1987-03-05 1989-04-18 Lencki Robert W J Method of producing microspheres
EP0283925A2 (fr) * 1987-03-19 1988-09-28 Boehringer Ingelheim Kg Procédé de purification de polyester résorbable
WO1992000342A1 (fr) * 1990-07-02 1992-01-09 Courtaulds Coatings (Holdings) Limited Compositions pulverulentes de revetement et procede de fabrication

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5342557A (en) * 1990-11-27 1994-08-30 United States Surgical Corporation Process for preparing polymer particles
EP0499205A2 (fr) * 1991-02-12 1992-08-19 United States Surgical Corporation Procédé pour préparer de particules de polymères bioabsorbables
EP0499205A3 (en) * 1991-02-12 1992-11-04 United States Surgical Corporation Process for preparing particles of bioabsorbable polymer
EP0574880A1 (fr) * 1992-06-15 1993-12-22 United States Surgical Corporation Procédé de traitement d'une matière d'implantation bioabsorbable
US5366756A (en) * 1992-06-15 1994-11-22 United States Surgical Corporation Method for treating bioabsorbable implant material
US5697976A (en) * 1992-06-15 1997-12-16 United States Surgical Corporation Bioabsorbable implant material
EP1044693A1 (fr) * 1997-12-29 2000-10-18 Takiron Co., Ltd. Une substance polymère biorésorbable, argileuse et collante
US6387391B1 (en) 1997-12-29 2002-05-14 Takiron Co., Ltd. Bioresorbable polymeric clayey and sticky substance
AU782328B2 (en) * 1999-04-16 2005-07-21 Takiron Co. Ltd. Bioresorbable polymeric clayey and sticky substance
WO2007054267A1 (fr) * 2005-11-10 2007-05-18 Airbus Deutschland Gmbh Procede de manipulation d'un liquide
EP1923187A1 (fr) * 2006-11-14 2008-05-21 Linde Aktiengesellschaft Dispositif et procédé pour la génération de particules
EP1923188A1 (fr) * 2006-11-14 2008-05-21 Linde Aktiengesellschaft Dispositif de production de particule
EP3040378A4 (fr) * 2013-08-29 2016-08-31 Lg Hausys Ltd Composition de résine à expanser pour feuille de mousse, feuille de mousse, procédé de production d'une résine d'acide polylactique particulaire, et procédé de fabrication d'une feuille de mousse
US10508176B2 (en) 2013-08-29 2019-12-17 Lg Hausys, Ltd. Foamable resin composition for foam sheet, foam sheet, process for preparing particulate polylactic acid and process for preparing foam sheet
JP2017504707A (ja) * 2014-07-17 2017-02-09 ウルトラ ヴイ カンパニー リミテッド フィラー用ポリジオキサノン粒子の製造方法

Also Published As

Publication number Publication date
DE69126766T2 (de) 1998-01-02
EP0488218A3 (en) 1992-08-12
EP0488218B1 (fr) 1997-07-09
US5342557A (en) 1994-08-30
CA2056055A1 (fr) 1992-05-28
DE69126766D1 (de) 1997-08-14

Similar Documents

Publication Publication Date Title
US5342557A (en) Process for preparing polymer particles
US5143662A (en) Process for preparing particles of bioabsorbable polymer
US5102983A (en) Process for preparing foamed, bioabsorbable polymer particles
Vert et al. More about the degradation of LA/GA-derived matrices in aqueous media
Nakamura et al. Bioabsorption of polylactides with different molecular properties
DE3708916C2 (fr)
Coombes et al. Gel casting of resorbable polymers: 1. Processing and applications
Mainil‐Varlet et al. Effect of in vivo and in vitro degradation on molecular and mechanical properties of various low‐molecular‐weight polylactides
CN109982728B (zh) 具有增强的成核速率的吸收性聚合物共混组合物
RU2583007C2 (ru) Биорассасывающиеся полимерные композиции, способы их обработки и изготовленные из них медицинские устройства
US5290494A (en) Process of making a resorbable implantation device
Eliaz et al. Characterization of a polymeric PLGA‐injectable implant delivery system for the controlled release of proteins
US6315788B1 (en) Composite materials and surgical articles made therefrom
Leenslag et al. Resorbable materials of poly (l‐lactide). V. Influence of secondary structure on the mechanical properties and hydrolyzability of poly (l‐lactide) fibers produced by a dry‐spinning method
CA2122670C (fr) Copolymeres en bloc absorbables et articles de chirurgie fabriques avec ces copolymeres
US5522841A (en) Absorbable block copolymers and surgical articles fabricated therefrom
RU2652180C2 (ru) Композиции, включающие смесь механически прочных рассасывающихся полимеров с точно управляемыми скоростями рассасывания, способы их обработки и продукты из них
US20060018948A1 (en) Biodegradable implantable medical devices, methods and systems
JP2008136849A (ja) 再生医学装置およびメルトブローン製造法
Nelson et al. Technique paper for wet-spinning poly (L-lactic acid) and poly (DL-lactide-co-glycolide) monofilament fibers
EP0195012A1 (fr) Implant article et son usage
EP0994736B1 (fr) Nouveau composite a base plastique et utilisation de ce composite
RU2689982C1 (ru) Композиции рассасывающихся полимеров, включающие смесь на основе сополимеров, полученных из моно- и двухфункциональных инициаторов полимеризации, технологические способы и медицинские устройства из этих композиций
Prabhu et al. Bioresorbable materials for orthopedic applications (Lactide and glycolide based)
Lee et al. Degradation behaviour in vitro for poly (D, L‐lactide‐co‐glycolide) as drug carrier

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): DE FR GB IT

PUAL Search report despatched

Free format text: ORIGINAL CODE: 0009013

AK Designated contracting states

Kind code of ref document: A3

Designated state(s): DE FR GB IT

17P Request for examination filed

Effective date: 19920909

17Q First examination report despatched

Effective date: 19940418

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): DE FR GB IT

REF Corresponds to:

Ref document number: 69126766

Country of ref document: DE

Date of ref document: 19970814

ITF It: translation for a ep patent filed

Owner name: UFFICIO BREVETTI RICCARDI & C.

ET Fr: translation filed
PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed
REG Reference to a national code

Ref country code: GB

Ref legal event code: IF02

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20101202

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20101126

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20101124

Year of fee payment: 20

Ref country code: IT

Payment date: 20101124

Year of fee payment: 20

REG Reference to a national code

Ref country code: DE

Ref legal event code: R071

Ref document number: 69126766

Country of ref document: DE

REG Reference to a national code

Ref country code: DE

Ref legal event code: R071

Ref document number: 69126766

Country of ref document: DE

REG Reference to a national code

Ref country code: GB

Ref legal event code: PE20

Expiry date: 20111126

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20111126

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20111128